Mi­cro­cap Capri­cor soars on in­ter­im PhII DMD da­ta show­ing func­tion­al ben­e­fit for old­er pa­tients

With the in­ter­im analy­sis for its Phase II Duchenne mus­cu­lar dy­s­tro­phy, lit­tle Capri­cor Ther­a­peu­tics was mere­ly look­ing for a guide­post, a sig­nal, a trend that the ef­fects seen in an ear­li­er tri­al can be repli­cat­ed with a new dos­ing reg­i­men and de­liv­ery method. In­stead, the biotech found it­self blessed with a bas­ket of da­ta points that seem to buck the nat­ur­al his­to­ry trend and sep­a­rate the drug from place­bo in a sta­tis­ti­cal­ly sig­nif­i­cant way, more than dou­bling its tiny stock $CAPR in pre-mar­ket trad­ing.

Lin­da Mar­bán Capri­cor

The pri­ma­ry end­point for the HOPE-2 tri­al is PUL 2.0, a mea­sure of up­per limb func­tion and one of sev­er­al ways Capri­cor quan­ti­fied skele­tal mus­cle im­prove­ment. Ex­ecs al­so spot­light­ed pul­monary and car­diac ben­e­fits in the top-line re­sults — fac­tors that are par­tic­u­lar­ly for the pa­tient pop­u­la­tion that they are tar­get­ing, who tend to be old­er and non-am­bu­la­to­ry.

Con­sist­ing of prog­en­i­tor cells de­rived from donor hearts, CAP-1002 is de­signed to re­lease ex­o­somes that kick off a cy­cle of mus­cle re­pair by sup­press­ing in­flam­ma­tion and dri­ving im­munomod­u­la­tion.

Cur­rent­ly, a num­ber of DMD pa­tients take glu­co­cor­ti­cos­teroids for that pur­pose, in­clud­ing pred­nisone and de­flaza­cort (sold in the US by Marathon as Em­flaza). There’s al­so Sarep­ta’s ex­on-skip­ping drug, eteplirsen (Ex­ondys 51), though its ben­e­fits have yet to be borne out; Sarep­ta and a hand­ful of ri­vals are now in hot pur­suit of a sup­posed one-time cure to re­place the miss­ing dy­s­trophin gene in pa­tients.

“While there had been ad­vances in gene ther­a­py, we be­lieve that con­trol­ling in­flam­ma­tion over and above what can be done by steroids is im­por­tant,” CEO Lin­da Mar­bán said in a con­fer­ence call.

Her hus­band, Ed­uar­do Mar­bán, had de­vel­oped the tech at Johns Hop­kins.

Da­ta from the small, place­bo-con­trolled study sug­gest that with a high­er dose than the past and de­liv­ered in­tra­venous­ly, the ther­a­py is work­ing. At the six-month cut, 6 pa­tients were evalu­able in each arm. For those treat­ed with CAP1002 mid-lev­el PUL — think mov­ing el­bows and pulling hand to mouth — de­te­ri­o­rat­ed by an av­er­age of 0.2 on a 6-point scale, com­pared to 0.8 on place­bo. The p-val­ue was 0.0389.

This and grip strength are the on­ly im­prove­ments still sta­tis­ti­cal­ly sig­nif­i­cant af­ter six months (there was al­so a three-month snap­shot), but Capri­cor stressed pos­i­tive trends through­out.

“I’d like to just re­mind peo­ple that this pop­u­la­tion of DMD re­al­ly rep­re­sents more than half of all DMD pa­tients and there re­al­ly have not been ther­a­pies that have re­al­ly fo­cused on this pop­u­la­tion which have just in­cred­i­bly high bur­den of dis­ease,” Craig Mc­Don­ald, the na­tion­al PI and a pro­fes­sor at UC Davis, said in the call.

On the key is­sue of safe­ty, Capri­cor not­ed that there had on­ly been one se­ri­ous ad­verse event among 30 in­fu­sions af­ter it put a stan­dard pre-med­ica­tion reg­i­men in place to mit­i­gate po­ten­tial im­mune re­ac­tions. Two pa­tients had had im­me­di­ate im­mune re­ac­tions to the treat­ment late last year, which prompt­ed the com­pa­ny to put a vol­un­tary hold on the tri­al.

Armed with these num­bers and an RMAT des­ig­na­tion from the FDA, Capri­cor is now look­ing in­to a “lean, ef­fi­cient” piv­otal study to po­si­tion the cell ther­a­py for a BLA — if it can find the cash to do so.

A few months ago it was forced to chop 21 staffers, or half of its work­force, in or­der to car­ry on with clin­i­cal ac­tiv­i­ties un­til the end of this year.

So­cial im­age: Shut­ter­stock

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

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